Nanocharacterization:Nanocharacterization:Goals, Challenges, and SolutionsGoals, Challenges, and Solutions

John Henry J. Scott

Microanalysis Research Group

Surface and Microanalysis Science Division

National Institute of Standards and Technology

National Nanotechnology Initiative Workshop

January 27, 2004

Levels of NanostructureLevels of Nanostructure

moleculesproteins

supramolecular complexesribosomes

organellesmitochondria

cellsliver cell

tissuesliver

1-10 nm 10-100 nm 100 nm - 1 m 1-10 m macro

3D structure

3D elemental

3D chemical

3D propertiesWant to Know

Supramolecular ComplexesSupramolecular Complexes

integrins mediate extra-cellular matrix interactions

tissue engineering

cancer

apoptosis

metastasize

Supramolecular ComplexesSupramolecular Complexes

mutant Ras found in 50% of all human

cancers

mutant Ras found in 90% of pancreatic

cancers

GPCRs

60% of all drugs

$60B/year

Protein MisfoldingProtein Misfolding

                  Dec 25, 2003

Disease Misfolded Protein

Alzheimer's amyloid

Parkinson's -Synuclein

Creutzfeld-Jakob,

mad-cow, kuru, scrapie...

(TSEs)

Prion protein (PrPsc)

Huntington's,

spinocerebellar ataxiasGlu repeats

MD, CF, ... various

rough ER

co-translational

importprotein sorting

& transport

Tissue EngineeringTissue Engineering

• $½ trillion per year lost to tissue damage• Liver transplants

• in US between 1987 and 1989

• 4,166 transplants (1,887 patients died)

• after 5 years, total cost = $960 million

• estimated cost of engineered liver = $50,000• plus $2,000/year for 5 years follow-up

• tissue-engineered artificial liver currently under development• outside the body• for temporary use

• Diabetes• cost = $120 billion/year

• artificial pancreas demonstrated experimentally

• estimated cost = $20,000

ChallengePossible Solution

coherent research, leverage

roadmapping

more info neededmultiple modalities,

multispectral, hyperspectral

extract knowledge, understanding from data

multivariate analysis, chemometrics

data integration informatics, XML

public concern, fear education, success

• infrastructure• standards• rôle for NIST?

EELS and EDS in the AEMEELS and EDS in the AEM

Upper Pole Piece

Lower Pole Piece

carbon substrate

copper grid bar

EDS Detector Snout

To EELS Spectrometer

bremsstrahlung

x-rays

Chemical Information from EELSChemical Information from EELS

Graphite

Diamond

Amorphous

Hyperspectral AnalysisHyperspectral Analysis

• guaranteed spatial registration of datasets• complementary information about the sample

x

y

E

x

y

E

EELS EDS

Multiple ModalitiesMultiple Modalities

Get data into and out of the system

ImportExport

Analyze Register

Fuse

Quantify

VisualizeData

Management

Analyze raw data and intermediate results:chemometricsclassificationSegmentationetc…

Image registration:- resolution matching,- aligning.

Map images to concentration

Integrate data from multiple modalities:Morphing,mapping

Flexible data visualization, presentation

Storing and accessing images and descriptive characteristics

Data FusionData Fusion

PVC/PMMA blend XPS+LSCMPVC/PMMA blend XPS+LSCM

bottom(LSCM)

top(XPS)

activeknowledge

mesh

Julia Fulghum, Univ New Mexico

Multivariate AnalysisMultivariate Analysis

Paul Kotula, Sandia National Labs

Multivariate AnalysisMultivariate Analysis

Multivariate AnalysisMultivariate Analysis

2-component model of color image

Original image

XML and InformaticsXML and Informatics

SampleComposition

InstrumentData

AnalyticalConditions

SpectrumData

SpectrumData

k-ratiosIntensitiesMLLSQ

ZAF(z)

MonteCarlo

Public Concern, FearPublic Concern, Fear

Jay Vacanti, 1997

gray goo problem

bio-artificial liver